Dorsalization of the neural tube by the non-neural ectoderm

The patterning of cell types along the dorsoventral axis of the spinal cord requires a complex set of inductive signals. While the chordamesoderm is a well-known source of ventralizing signals, relatively little is known about the cues that induce dorsal cell types, including neural crest. Here, we demonstrate that juxtaposition of the non-neural and neural ectoderm is sufficient to induce the expression of dorsal markers, Wnt-1, Wnt-3a and Slug, as well as the formation of neural crest cells. In addition, the competence of neural plate to express Wnt-1 and Wnt-3a appears to be stage dependent, occurring only when neural tissue is taken from stage 8–10 embryos but not from stage 4 embryos, regardless of the age of the non-neural ectoderm. In contrast to the induction of Wnt gene expression, neural crest cell formation and Slug expression can be induced when either stage 4 or stage 8–10 neural plates are placed in contact with the non-neural ectoderm. These data suggest that the non-neural ectoderm provides a signal (or signals) that specifies dorsal cell types within the neural tube, and that the response is dependent on the competence of the neural tissue

Survival of Hendra Virus in the Environment: Modelling the Effect of Temperature

Hendra virus (HeV), a highly pathogenic zoonotic paramyxovirus recently emerged from bats, is a major concern to the horse industry in Australia. Previous research has shown that higher temperatures led to lower virus survival rates in the laboratory. We develop a model of survival of HeV in the environment as influenced by temperature. We used 20 years of daily temperature at six locations spanning the geographic range of reported HeV incidents to simulate the temporal and spatial impacts of temperature on HeV survival. At any location, simulated virus survival was greater in winter than in summer, and in any month of the year, survival was higher in higher latitudes. At any location, year-to-year variation in virus survival 24 h post-excretion was substantial and was as large as the difference between locations. Survival was higher in microhabitats with lower than ambient temperature, and when environmental exposure was shorter. The within-year pattern of virus survival mirrored the cumulative within-year occurrence of reported HeV cases, although there were no overall differences in survival in HeV case years and non-case years. The model examines the effect of temperature in isolation; actual virus survivability will reflect the effect of additional environmental factor

Survival of Hendra Virus in the Environment: Modelling the Effect of Temperature

Hendra virus (HeV), a highly pathogenic zoonotic paramyxovirus recently emerged from bats, is a major concern to the horse industry in Australia. Previous research has shown that higher temperatures led to lower virus survival rates in the laboratory. We develop a model of survival of HeV in the environment as influenced by temperature. We used 20 years of daily temperature at six locations spanning the geographic range of reported HeV incidents to simulate the temporal and spatial impacts of temperature on HeV survival. At any location, simulated virus survival was greater in winter than in summer, and in any month of the year, survival was higher in higher latitudes. At any location, year-to-year variation in virus survival 24 h post-excretion was substantial and was as large as the difference between locations. Survival was higher in microhabitats with lower than ambient temperature, and when environmental exposure was shorter. The within-year pattern of virus survival mirrored the cumulative within-year occurrence of reported HeV cases, although there were no overall differences in survival in HeV case years and non-case years. The model examines the effect of temperature in isolation; actual virus survivability will reflect the effect of additional environmental factor

Serologic evidence for the presence in Pteropus bats of a paramyxovirus related to equine morbillivirus.

Two outbreaks of a previously unknown disease in horses and humans occurred in Queensland in 1994. The outbreaks occurred within 1 month of each other in Brisbane and Mackay, which are approximately 1000 km apart. In the Brisbane incident, 21 horses were infected of which 14 died or were euthanized after severe clinical signs of an acute respiratory disease. Two human cases were in patients with less well defined clinical signs; one patient died (1,2). In the Mackay incident two horses became seriously ill and died, and one person also died (3). Although it is now known that the two outbreaks occurred in August and September 1994, knowledge of the Mackay outbreak did not occur until late 1995 when the infected person died of a relapsing encephalitis. The name equine morbillivirus (EMV) has been proposed for a paramyxovirus isolated from four of the Brisbane horses and the first patient who died (2)

The cdx Genes and Retinoic Acid Control the Positioning and Segmentation of the Zebrafish Pronephros

Kidney function depends on the nephron, which comprises a blood filter, a tubule that is subdivided into functionally distinct segments, and a collecting duct. How these regions arise during development is poorly understood. The zebrafish pronephros consists of two linear nephrons that develop from the intermediate mesoderm along the length of the trunk. Here we show that, contrary to current dogma, these nephrons possess multiple proximal and distal tubule domains that resemble the organization of the mammalian nephron. We examined whether pronephric segmentation is mediated by retinoic acid (RA) and the caudal (cdx) transcription factors, which are known regulators of segmental identity during development. Inhibition of RA signaling resulted in a loss of the proximal segments and an expansion of the distal segments, while exogenous RA treatment induced proximal segment fates at the expense of distal fates. Loss of cdx function caused abrogation of distal segments, a posterior shift in the position of the pronephros, and alterations in the expression boundaries of raldh2 and cyp26a1, which encode enzymes that synthesize and degrade RA, respectively. These results suggest that the cdx genes act to localize the activity of RA along the axis, thereby determining where the pronephros forms. Consistent with this, the pronephric-positioning defect and the loss of distal tubule fate were rescued in embryos doubly-deficient for cdx and RA. These findings reveal a novel link between the RA and cdx pathways and provide a model for how pronephric nephrons are segmented and positioned along the embryonic axis

Structure-activity relationship study and optimisation of 2-aminopyrrole-1-benzyl-4,5-diphenyl-1H-pyrrole-3-carbonitrile as a broad spectrum metallo-β-lactamase inhibitor

A SAR study on derivatives of 2-amino-1-benzyl-4,5-diphenyl-1H-pyrrole-3-carbonitrile 5a revealed that the 3-carbonitrile group, vicinal 4,5-diphenyl and N-benzyl side chains of the pyrrole are important for the inhibitory potencies of these compounds against members representing the three main subclasses of metallo-β-lactamases (MBLs), i.e. IMP-1 (representing the B1 subgroup), CphA (B2) and AIM-1 (B3). Coupling of 5a with a series of acyl chlorides and anhydrides led to the discovery of two N-acylamide derivatives, 10 and 11, as the two most potent IMP-1 inhibitors in this series. However, these compounds are less effective towards CphA and AIM-1. The N-benzoyl derivative of 5a retained potent in\ua0vitro activity against each of MBLs tested (with inhibition constants in the low μM range). Importantly, this compound also significantly enhanced the sensitivity of IMP-1, CphA- or AIM-1-producing cell cultures towards meropenem. This compound presents a promising starting point for the development of a universal MBL inhibitor, targeting members of each of the major subgroups of this family of enzymes

The MUMBA campaign: measurements of urban, marine and biogenic air

The Measurements of Urban, Marine and Biogenic Air (MUMBA) campaign took place in Wollongong, New South Wales (a small coastal city approximately 80 km south of Sydney, Australia) from 21 December 2012 to 15 February 2013. Like many Australian cities, Wollongong is surrounded by dense eucalyptus forest, so the urban airshed is heavily influenced by biogenic emissions. Instruments were deployed during MUMBA to measure the gaseous and aerosol composition of the atmosphere with the aim of providing a detailed characterisation of the complex environment of the ocean–forest–urban interface that could be used to test the skill of atmospheric models. The gases measured included ozone, oxides of nitrogen, carbon monoxide, carbon dioxide, methane and many of the most abundant volatile organic compounds. The aerosol characterisation included total particle counts above 3 nm, total cloud condensation nuclei counts, mass concentration, number concentration size distribution, aerosol chemical analyses and elemental analysis. The campaign captured varied meteorological conditions, including two extreme heat events, providing a potentially valuable test for models of future air quality in a warmer climate. There was also an episode when the site sampled clean marine air for many hours, providing a useful additional measure of the background concentrations of these trace gases within this poorly sampled region of the globe. In this paper we describe the campaign, the meteorology and the resulting observations of atmospheric composition in general terms in order to equip the reader with a sufficient understanding of the Wollongong regional influences to use the MUMBA datasets as a case study for testing a chemical transport model. © Author(s) 2017.The data are available from PANGAEA (http://doi.pangaea.de/10.1594/PANGAEA.871982)