Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions.

The demands of cancer cell proliferation alongside an inadequate angiogenic response lead to insufficient oxygen availability in the tumor microenvironment. Within the mitochondria, oxygen is the major electron acceptor for NADH, with the result that the reducing potential produced through tricarboxylic acid (TCA) cycle activity and mitochondrial respiration are functionally linked. As the oxidizing activity of the TCA cycle is required for efficient synthesis of anabolic precursors, tumoral hypoxia could lead to a cessation of proliferation without another means of correcting the redox imbalance.

Genomic insights into the metabolism of 'Candidatus Defluviicoccus seviourii', a member of Defluviicoccus cluster III abundant in industrial activated sludge.

Filamentous cluster III Defluviicoccus (DF3) are known to proliferate and cause bulking issues in industrial wastewater treatment plants. Members of the genus Defluviicoccus are also known to exhibit the glycogen accumulating organism (GAO) phenotype, which is suggested to be detrimental to enhanced biological phosphorus removal (EBPR). Despite the reported negative impact members of the DF3 have on activated sludge wastewater treatment systems, limited research has focused on understanding the physiological traits that allow them to compete in these environments.

Verteporfin selectively kills hypoxic glioma cells through iron-binding and increased production of reactive oxygen species.

Gliomas are highly malignant brain tumours characterised by extensive areas of poor perfusion which subsequently leads to hypoxia and reduced survival. Therapies that address the hypoxic microenvironment are likely to significantly improve patient outcomes. Verteporfin, a benzoporphyrin-like drug, has been suggested to target the Yes-associated protein (YAP).

Genomic and Analyses Reveal the spp. as Abundant Fermentative Glycogen Accumulating Organisms in Enhanced Biological Phosphorus Removal Systems.

Enhanced biological phosphorus removal (EBPR) involves the cycling of biomass through carbon-rich (feast) and carbon-deficient (famine) conditions, promoting the activity of polyphosphate accumulating organisms (PAOs). However, several alternate metabolic strategies, without polyphosphate storage, are possessed by other organisms, which can compete with the PAO for carbon at the potential expense of EBPR efficiency. The most studied are the glycogen accumulating organisms (GAOs), which utilize aerobically stored glycogen to energize anaerobic substrate uptake and storage.

Oncogenic IDH1 Mutations Promote Enhanced Proline Synthesis through PYCR1 to Support the Maintenance of Mitochondrial Redox Homeostasis.

Since the discovery of mutations in isocitrate dehydrogenase 1 (IDH1) in gliomas and other tumors, significant efforts have been made to gain a deeper understanding of the consequences of this oncogenic mutation. One aspect of the neomorphic function of the IDH1 R132H enzyme that has received less attention is the perturbation of cellular redox homeostasis. Here, we describe a biosynthetic pathway exhibited by cells expressing mutant IDH1.

Managing the excessive proliferation of glycogen accumulating organisms in industrial activated sludge by nitrogen supplementation: A FISH-NanoSIMS approach.

Defluviicoccus vanus-related glycogen accumulating organisms (GAO) regularly proliferate in industrial wastewater treatment plants handling high carbon but nitrogen deficient wastes. When GAO dominate, they are associated with poor performance, characterised by slow settling biomass and turbid effluents. Although their ecophysiology has been studied thoroughly in domestic waste treatment plants, little attention has been paid to them in aerobic industrial systems.

Remediation of Thiothrix spp. associated bulking problems by raw wastewater feeding: A full-scale experience.

An industrial wastewater treatment plant (WWTP) in Australia has long suffered from bulking problems associated with the proliferation of Thiothrix spp. The WWTP consists of a covered anaerobic lagoon (CAL) followed by a sequencing batch reactor (SBR). The CAL functions as both an anaerobic digester and surge lagoon for the irregular flow of wastewater generated from the production of seasonal products.

Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma.

Multiple myeloma (MM), an incurable plasma cell malignancy, requires localisation within the bone marrow. This microenvironment facilitates crucial interactions between the cancer cells and stromal cell types that permit the tumour to survive and proliferate. There is increasing evidence that the bone marrow mesenchymal stem cell (BMMSC) is stably altered in patients with MM-a phenotype also postulated to exist in patients with monoclonal gammopathy of undetermined significance (MGUS) a benign condition that precedes MM.

Hypoxia and metabolic adaptation of cancer cells.

Low oxygen tension (hypoxia) is a pervasive physiological and pathophysiological stimulus that metazoan organisms have contended with since they evolved from their single-celled ancestors. The effect of hypoxia on a tissue can be either positive or negative, depending on the severity, duration and context. Over the long-term, hypoxia is not usually consistent with normal function and so multicellular organisms have had to evolve both systemic and cellular responses to hypoxia.

The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility.

The interplay between long-term potentiation and long-term depression (LTD) is thought to be involved in learning and memory formation. One form of LTD expressed in the hippocampus is initiated by the activation of the group 1 metabotropic glutamate receptors (mGluRs). Importantly, mGluRs have been shown to be critical for acquisition of new memories and for reversal learning, processes that are thought to be crucial for cognitive flexibility.

Acute Q fever in northern Queensland: variation in incidence related to rainfall and geographical location.

The aims of this study were to define the basic epidemiology of serologically confirmed acute Q fever in patients tested via the Townsville Hospital laboratory from 2000 to 2010 and to determine the impact of geographical location and seasonality on the incidence of acute cases in the Townsville region. Seven Statistical Local Areas (SLA) were identified as having an incidence higher than the average Queensland incidence over the study period. The SLA with the highest incidence was Woodstock-Ross with 24.

The Role of p38 MAPK and Its Substrates in Neuronal Plasticity and Neurodegenerative Disease.

A significant amount of evidence suggests that the p38-mitogen-activated protein kinase (MAPK) signalling cascade plays a crucial role in synaptic plasticity and in neurodegenerative diseases. In this review we will discuss the cellular localisation and activation of p38 MAPK and the recent advances on the molecular and cellular mechanisms of its substrates: MAPKAPK 2 (MK2) and tau protein. In particular we will focus our attention on the understanding of the p38 MAPK-MK2 and p38 MAPK-tau activation axis in controlling neuroinflammation, actin remodelling and tau hyperphosphorylation, processes that are thought to be involved in normal ageing as well as in neurodegenerative diseases.

Brucellosis in northern Australia.

The aim of this study was to define the clinical presentation of brucellosis in northern Australia and to assess the long-term impact of brucellosis on individual lives. A retrospective review was conducted to assess 32 patients with brucellosis caused by Brucella suis in Townsville, Australia during 1996-2009. All patients were Caucasian males with a mean age of 35 years.

Ecophysiology of the Actinobacteria in activated sludge systems.

This review considers what is known about the Actinobacteria in activated sludge systems, their abundance and their functional roles there. Participation in processes leading to the microbiological removal of phosphate and in the operational problems of bulking and foaming are discussed in terms of their ecophysiological traits. We consider critically whether elucidation of their nutritional requirements and other physiological properties allow us to understand better what might affect their survival capabilities in these highly competitive systems.

Ecophysiology of mycolic acid-containing Actinobacteria (Mycolata) in activated sludge foams.

Increasing incidences of activated sludge foaming have been reported in the last decade in Danish plants treating both municipal and industrial wastewaters. In most cases, foaming is caused by the presence of Actinobacteria; branched mycolic acid-containing filaments (the Mycolata) and the unbranched Candidatus'Microthix parvicella'. Surveys from wastewater treatment plants revealed that the Mycolata were the dominant filamentous bacteria in the foam.

Gordonia defluvii sp. nov., an actinomycete isolated from activated sludge foam.

Three strains of non-motile, Gram-positive, filamentous actinomycetes, isolates J4(T), J5 and J59, initially recognized microscopically in activated sludge foam by their distinctive branching patterns, were isolated by micromanipulation. The taxonomic positions of the isolates were determined using a polyphasic approach. Almost-complete 16S rRNA gene sequences of the isolates were aligned with corresponding sequences of representatives of the suborder Corynebacterineae and phylogenetic trees were inferred using three tree-making algorithms.

The in situ physiology of Skermania piniformis in foams in Australian activated sludge plants.

The in situ physiology of the filamentous bacterium Skermania piniformis frequently seen in activated sludge foams in Australia was investigated. An oligonucleotide probe, Spin1449, targeting the 16S rRNA of S. piniformis was designed for its identification by fluorescence in situ hybridization (FISH), validated with pure cultures and applied successfully to foam samples from two geographically distant Australian plants.

The in situ physiology of "Nostocoida limicola" II, a filamentous bacterial morphotype in bulking activated sludge, using fluorescence in situ hybridization and microautoradiography.

The in situ physiology of the actinobacterial bulking and foaming filamentous bacterium "Nostocoida limicola" II was studied by fluorescence in situ hybridization/microautoradiography. Substrate assimilation patterns of pure cultures of this bacterium were different to those seen in activated sludge biomass samples. There was no evidence to suggest that "N.

Substrate uptake by Gordonia amarae in activated sludge foams by FISH-MAR.

Gordonia amarae is a right-angled branching filament belonging to the mycolic acid-containing Actinobacteria which is commonly found in many foaming activated sludge wastewater treatment plants. Although studies on different substrates as sole carbon sources by pure cultures of G. amarae have been carried out, none have examined substrate uptake by this organism in situ.

Millisia brevis gen. nov., sp. nov., an actinomycete isolated from activated sludge foam.

The taxonomic position of two mycolic-acid-producing actinomycetes, isolates J81T and J82, which were recovered from activated sludge foam, was clarified. Comparative 16S rRNA gene sequence studies indicated that the organisms formed a distinct lineage within the Corynebacterineae 16S rRNA gene tree. The taxonomic integrity of this group was underpinned by a wealth of phenotypic data, notably characteristic rudimentary right-angled branching.

Improved permeabilization protocols for fluorescence in situ hybridization (FISH) of mycolic-acid-containing bacteria found in foams.

Formation of thick, stable foams and scums on activated sludge wastewater treatment plants is a worldwide problem, and to better understand what causes this foam and to cure it, there is a need to identify and quantify the bacteria present there. Fluorescence in situ hybridisation (FISH) overcomes the difficulties experienced with microscopic methods of identification for the mycolic-acid-containing actinomycetes (the mycolata), which are present in foams, where many share the morphotype of right-angled branching filaments. However, the presence of hydrophobic mycolic acids in their cell wall makes this group of bacteria particularly difficult to permeabilise, which greatly reduces the usefulness of FISH.

The large PAO cells in full-scale EBPR biomass samples are not yeast spores but possibly novel members of the beta-Proteobacteria.

Large, homogenous clusters of coccobacilli were found to be abundant in the biomasses from a conventional plant at Rosebud, Victoria, Australia. The identity and the in situ physiology of these dominant microorganisms were investigated in this study. These large clustered cells were revealed to be neither Gram positive nor Gram negative bacteria and contain polyP granules.