A nitrite-oxidising bacterium constitutively consumes atmospheric hydrogen.

Chemolithoautotrophic nitrite-oxidising bacteria (NOB) of the genus Nitrospira contribute to nitrification in diverse natural environments and engineered systems. Nitrospira are thought to be well-adapted to substrate limitation owing to their high affinity for nitrite and capacity to use alternative energy sources. Here, we demonstrate that the canonical nitrite oxidiser Nitrospira moscoviensis oxidises hydrogen (H) below atmospheric levels using a high-affinity group 2a nickel-iron hydrogenase [K = 32 nM].

Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy.

Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) are attractive drug targets, and we present class I and II aaRSs as previously unrecognized targets for adenosine 5'-monophosphate-mimicking nucleoside sulfamates. The target enzyme catalyzes the formation of an inhibitory amino acid-sulfamate conjugate through a reaction-hijacking mechanism. We identified adenosine 5'-sulfamate as a broad-specificity compound that hijacks a range of aaRSs and ML901 as a specific reagent a specific reagent that hijacks a single aaRS in the malaria parasite , namely tyrosine RS (YRS).

The First Hybrid International Educational Comprehensive Cleft Care Workshop.

Objective: Describe the first hybrid global simulation-based comprehensive cleft care workshop, evaluate impact on participants, and compare experiences based on in-person versus virtual attendance.

Design: Cross-sectional survey-based evaluation.

Setting: International comprehensive cleft care workshop.

Design of proteasome inhibitors with oral efficacy in vivo against and selectivity over the human proteasome.

The proteasome is a potential antimalarial drug target. We have identified a series of amino-amide boronates that are potent and specific inhibitors of the 20S proteasome (20S) β5 active site and that exhibit fast-acting antimalarial activity. They selectively inhibit the growth of compared with a human cell line and exhibit high potency against field isolates of and They have a low propensity for development of resistance and possess liver stage and transmission-blocking activity.

A Clinical Report Utilizing the VITOM 3D Microvideoscope for Cleft Palate Repair.

Cleft palate surgery has traditionally presented numerous problems for cleft surgeons including ergonomics, limited visual fields restricting the opportunity for demonstration and teaching. Additionally, the move toward online teaching means the ability to record or livestream video is paramount. The following report of eight cleft palate repairs highlights the novel use of the Vitom 3D microvideoscope as an innovative technique for cleft palate repair with our early experience demonstrating significant ergonomic and teaching benefits.

High Throughput Screening to Identify Selective and Nonpeptidomimetic Proteasome Inhibitors As Antimalarials.

The Ubiquitin Proteasome System is the main proteolytic pathway in eukaryotic cells, playing a role in key cellular processes. The essentiality of the proteasome is well validated, underlying its potential as an antimalarial target, but selective compounds are required to avoid cytotoxic effects in humans. Almost 550000 compounds were tested for the inhibition of the chymotrypsin-like activity of the proteasome using a Proteasome-GLO luminescence assay.

Benthic habitat condition of the continental shelf surrounding oil and gas platforms in the Santa Barbara Channel, Southern California.

The continental shelf of southern California is an important location for the extraction of petroleum and natural gas. Many platforms in the region have been operating for more than four decades and are being targeted for decommissioning. Information on the condition of surrounding habitats to the platforms will be important for regulators.

Cellular and Structural Basis of Synthesis of the Unique Intermediate Dehydro-F-0 in Mycobacteria.

F is a low-potential redox cofactor used by diverse bacteria and archaea. In mycobacteria, this cofactor has multiple roles, including adaptation to redox stress, cell wall biosynthesis, and activation of the clinical antitubercular prodrugs pretomanid and delamanid. A recent biochemical study proposed a revised biosynthesis pathway for F in mycobacteria; it was suggested that phosphoenolpyruvate served as a metabolic precursor for this pathway, rather than 2-phospholactate as long proposed, but these findings were subsequently challenged.

A Review of 30 Years of Alveolar Bone Grafting in the Mixed Dentition Using a Standardized Protocol in Western Australia.

Background: Outcomes for a continuously applied alveolar bone grafting protocol, established in 1982, are reported and compared to previously published outcomes from the authors' unit and elsewhere.

Methods: A descriptive, retrospective cohort study of alveolar bone grafting outcomes at a tertiary referral cleft center was performed. Records of all alveolar bone grafts between 2002 and 2014 were reviewed (224 grafts).

Decreased K13 Abundance Reduces Hemoglobin Catabolism and Proteotoxic Stress, Underpinning Artemisinin Resistance.

Increased tolerance of Plasmodium falciparum to front-line artemisinin antimalarials (ARTs) is associated with mutations in Kelch13 (K13), although the precise role of K13 remains unclear. Here, we show that K13 mutations result in decreased expression of this protein, while mislocalization of K13 mimics resistance-conferring mutations, pinpointing partial loss of function of K13 as the relevant molecular event. K13-GFP is associated with ∼170 nm diameter doughnut-shaped structures at the parasite periphery, consistent with the location and dimensions of cytostomes.

Selecting Comparator Sites for Ecological Causal Assessment Based on Expected Biological Similarity.

Sites in poor ecological condition often require causal assessment to determine appropriate follow-up actions. Site-specific causal assessments can be time consuming. To streamline the process, we describe a quantitative method that expedites a key component of causal assessment: identifying a group of ecologically similar (comparator) sites that are used to compare and contrast biological condition and stressor exposure at the site of interest.

Organic contaminants as an ecological tool to explore niche partitioning: a case study using three pelagic shark species.

Chemical contaminant profiles are linked to an animal's niche, providing a potential tool by which to assess resource partitioning in pelagic species. As proof of concept, we examined contaminant signatures in three species of sharks (Isurus oxyrinchus, Prionace glauca, and Alopias vulpinus) known to overlap in both space and time. Since these sharks comprise a predatory guild within the Southern California Bight (SCB), we predicted that species may partition spatial and dietary resources to limit the extent of competitive exclusion.

The structure of the PA28-20S proteasome complex from Plasmodium falciparum and implications for proteostasis.

The activity of the proteasome 20S catalytic core is regulated by protein complexes that bind to one or both ends. The PA28 regulator stimulates 20S proteasome peptidase activity in vitro, but its role in vivo remains unclear. Here, we show that genetic deletion of the PA28 regulator from Plasmodium falciparum (Pf) renders malaria parasites more sensitive to the antimalarial drug dihydroartemisinin, indicating that PA28 may play a role in protection against proteotoxic stress.

A Low-Cost Continuous Turbidity Monitor.

Turbidity describes the cloudiness, or clarity, of a liquid. It is a principal indicator of water quality, sensitive to any suspended solids present. Prior work has identified the lack of low-cost turbidity monitoring as a significant hurdle to overcome to improve water quality in many domains, especially in the developing world.

Species-Specific Characteristics Influence Contaminant Accumulation Trajectories and Signatures Across Ontogeny in Three Pelagic Shark Species.

Factors influencing organic contaminant accumulation in sharks, especially across ontogeny, are not well-known. Contaminant concentrations were measured in three species of sharks (Blue, Shortfin Mako, and Common Thresher) across a range of size classes (neonatal to adult) that vary in their ecological and physiological characteristics. Empirical data was compared to a theoretical framework that predicted the shape of lifetime accumulation curves.

Target Validation and Identification of Novel Boronate Inhibitors of the Plasmodium falciparum Proteasome.

The Plasmodium proteasome represents a potential antimalarial drug target for compounds with activity against multiple life cycle stages. We screened a library of human proteasome inhibitors (peptidyl boronic acids) and compared activities against purified P. falciparum and human 20S proteasomes.

Artemisinin kills malaria parasites by damaging proteins and inhibiting the proteasome.

Artemisinin and its derivatives (collectively referred to as ARTs) rapidly reduce the parasite burden in Plasmodium falciparum infections, and antimalarial control is highly dependent on ART combination therapies (ACTs). Decreased sensitivity to ARTs is emerging, making it critically important to understand the mechanism of action of ARTs. Here we demonstrate that dihydroartemisinin (DHA), the clinically relevant ART, kills parasites via a two-pronged mechanism, causing protein damage, and compromising parasite proteasome function.

Adaptation and application of multivariate AMBI (M-AMBI) in US coastal waters.

The multivariate AMBI (M-AMBI) is an extension of the AZTI Marine Biotic Index (AMBI) that has been used extensively in Europe, but not in the United States. In a previous study, we adapted AMBI for use in US coastal waters (US AMBI), but saw biases in salinity and score distribution when compared to locally calibrated indices. In this study we modified M-AMBI for US waters and compared its performance to that of US AMBI.

Our experience in using telehealth for paediatric plastic surgery in Western Australia.

Background: Western Australia accounts for one-third of Australia's total land mass. Princess Margaret Hospital is the only dedicated plastic surgery tertiary referral centre providing services to over 500 000 children across the state. The aim of this study is to share our experience using telehealth for service provision and delivery of care in a geographically challenging setting.

Hospitalisations up to adulthood for children born with orofacial clefts.

Aim: The aim of this study was to compare hospital admissions from infancy to adulthood, between children born with orofacial clefts (OFC) and those without OFC.

Methods: The method used was a cohort study using record-linked administrative datasets. Participants included all children liveborn in Western Australia (WA) between 1980 and 2010 diagnosed with OFC, who were frequency matched by year of birth to randomly selected liveborn children without OFC.

Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome.

Aims: Triple-negative breast cancer (TNBC) patients generally have a poor outcome; there is a pressing need to identify more effective therapeutic strategies. Clinical trials targeting programmed death 1/programmed death ligand 1 (PD1/PDL1) in melanoma and non-small-cell lung cancer have reported high response rates, and tumoral PDL1 expression has been suggested as a potential biomarker to enrich for patient response to these treatments. There are only very limited data to date reporting the expression of PDL1 in TNBC.

Poor survival of females with bladder cancer is limited to those aged 70 years or over: a population-wide linkage study, New South Wales, Australia.

Although men are diagnosed with bladder cancer (BC) with a rate three times higher than women, women experience poorer survival. The cause of this gender difference is not clear. The aim of this study was to investigate the discrepancy in survival from BC by gender and explore potential explanations for the difference using a population-wide linkage study.

Phenotyping: targeting genotype's rich cousin for diagnosis.

There are many current and evolving tools to assist clinicians in their daily work of phenotyping. In medicine, the term 'phenotype' is usually taken to mean some deviation from normal morphology, physiology and behaviour. It is ascertained via history, examination and investigations, and a primary aim is diagnosis.

Tubular carcinoma of the breast: axillary involvement and prognostic factors.

Background: Tubular carcinoma (TC) of the breast has a very favourable prognosis. The role for axillary staging in small TC was questioned. This study investigated the frequency of axillary metastases and prognostic factors in pure TC of the breast.