Ben Maslen

The advent of massively parallel sequencing revealed extensive transcription beyond protein-coding genes, identifying tens of thousands of long noncoding RNAs (lncRNAs). Selected functional examples raised the possibility that lncRNAs, as a class, may maintain broad regulatory roles. Expression of lncRNAs is strongly linked with adjacent protein-coding gene expression, suggesting potential cis-regulatory functions. A more detailed understanding of these regulatory roles may be obtained through careful examination of the precise timing of lncRNA expression relative to adjacent protein-coding genes. Despite the diversity of reported lncRNA regulatory mechanisms, where causal cis-regulatory relationships exist, lncRNA transcription is expected to precede changes in target gene expression. Using a high temporal resolution RNA-seq time course, we profiled the expression dynamics of several thousand lncRNAs and protein-coding genes in synchronized, transitioning human cells. Our findings ...

Background The advent of next-generation sequencing revealed extensive transcription beyond protein-coding genes, identifying tens of thousands of long non-coding RNAs (lncRNAs). Selected functional examples raised the possibility that lncRNAs, as a class, may maintain broad regulatory roles. Compellingly, lncRNA expression is strongly linked with adjacent protein-coding gene expression, suggesting a potential cis-regulatory function. Evidence for these regulatory roles may be obtained through careful examination of the precise timing of lncRNA expression relative to adjacent protein-coding genes. Results Where causal cis-regulatory relationships exist, lncRNA activation is expected to precede changes in adjacent target gene expression. Using an RNA-seq time course of uniquely high temporal resolution, we profiled the expression dynamics of several thousand lncRNAs and protein-coding genes in synchronized, transitioning human cells. Our findings reveal lncRNAs are expressed synchronously with adjacent protein-coding genes. Analysis of lipopolysaccharide-activated mouse dendritic cells revealed the same temporal relationship observed in transitioning human cells. Conclusion Our findings suggest broad-scale cis-regulatory roles for lncRNAs are not common. The strong association between lncRNAs and adjacent genes may instead indicate an origin as transcriptional by-products from active protein-coding gene promoters and enhancers.

Otoliths are commonly used to discriminate between fish stocks, through both elemental composition and otolith shape. Typical studies also have a large number of elemental compositions and shape measures relative to the number of otolith samples, with these measures exhibiting strong mean–variance relationships. These properties make otolith composition and shape data highly suitable for use within a multivariate generalised linear model (MGLM) framework, yet MGLMs have never been applied to otolith data. Here we apply both a traditional distance based permutational multivariate analysis of variance (PERMANOVA) and MGLMs to a case study of striped snakehead (Channa striata) in India. We also introduce the Tweedie and gamma distributions as suitable error structures for the MGLMs, drawing similarities to the properties of Biomass data. We demonstrate that otolith elemental data and combined otolith elemental and shape data violate the assumption of homogeneity of variance of PERMANOV...

Adjuvant chemotherapy for stage II colon cancer is a controversial area with treatment often reserved for patients with high‐risk clinicopathological features. The aim of this study was to characterize which patients with stage II disease were offered adjuvant chemotherapy in an Australian and New Zealand setting.

Blue whales were brought to the edge of extinction by commercial whaling in the twentieth century and their recovery rate in the Southern Hemisphere has been slow; they remain endangered. Blue whales, although the largest animals on Earth, are difficult to study in the Southern Hemisphere, thus their population structure, distribution and migration remain poorly known. Fortunately, blue whales produce powerful and stereotyped songs, which prove an effective clue for monitoring their different ‘acoustic populations.’ The DGD-Chagos song has been previously reported in the central Indian Ocean. A comparison of this song with the pygmy blue and Omura’s whale songs shows that the Chagos song are likely produced by a distinct previously unknown pygmy blue whale population. These songs are a large part of the underwater soundscape in the tropical Indian Ocean and have been so for nearly two decades. Seasonal differences in song detections among our six recording sites suggest that the Cha...

BACKGROUND AND AIM Identification of the most appropriate population pharmacokinetic model-based Bayesian estimation is required prior to its implementation in routine clinical practice to inform tacrolimus dosing decisions. This study aimed to determine the predictive performances of relevant population pharmacokinetic models of tacrolimus developed from various solid organ transplant recipient populations in adult heart transplant recipients, stratified based on concomitant azole antifungal use. Concomitant azole antifungal therapy alters tacrolimus pharmacokinetics substantially necessitating dose adjustments. METHODS Population pharmacokinetic models of tacrolimus were selected (n=17) for evaluation from a recent systematic review. The models were transcribed and implemented in NONMEM version 7.4.3. Data from 85 heart transplant recipients (2387 tacrolimus concentrations) administered the oral immediate-release formulation of tacrolimus (Prograf®) were obtained up to 391 days post-transplant. The performance of each model was evaluated using (1) prediction-based assessment (bias and imprecision) of the individual predicted tacrolimus concentration of the fourth dosing occasion (MAXEVAL=0, FOCE-I) from 1-3 prior dosing occasions and (2) simulation-based assessment (prediction-corrected visual predictive check, pcVPC). Both assessments were stratified based on concomitant azole antifungal use. RESULTS Regardless of the number of prior dosing occasions (1-3) and concomitant azole antifungal use, all models demonstrated unacceptable individual predicted tacrolimus concentration of the fourth dosing occasion (n=152). The pcVPC graphics indicated these models inadequately predicted observed tacrolimus concentrations. CONCLUSIONS All models evaluated were unable to adequately describe tacrolimus pharmacokinetics in adult heart transplant recipients included in this study. Further work is required to describe tacrolimus pharmacokinetics for our heart transplant recipient cohort.

Eyespots evolved independently in many taxa as anti-predator signals. There remains debate regarding whether eyespots function as diversion targets, predator mimics, conspicuous startling signals, deceptive detection, or a combination. Although eye patterns and gaze modify human behaviour, anti-predator eyespots do not occur naturally in contemporary mammals. Here we show that eyespots painted on cattle rumps were associated with reduced attacks by ambush carnivores (lions and leopards). Cattle painted with eyespots were significantly more likely to survive than were cross-marked and unmarked cattle, despite all treatment groups being similarly exposed to predation risk. While higher survival of eyespot-painted cattle supports the detection hypothesis, increased survival of cross-marked cattle suggests an effect of novel and conspicuous marks more generally. To our knowledge, this is the first time eyespots have been shown to deter large mammalian predators. Applying artificial mark...

Pelagic biofoulers such as barnacles or bryozoans settle and raft on natural debris like pumice or seeds. Recent influxes of marine debris into the world’s oceans, especially plastic, have increased habitat availability for these biofoulers. Goose barnacles in the genus Lepas are some of the most common biofouling taxa globally, and play an important role in biofouling communities as foundation species. We examined community succession, growth rates and isotopic composition in Lepas and their associated biofouling communities in coastal waters of eastern Australia. Community succession on a fixed surface mooring showed an increase in species diversity over 25 weeks. Using the abundances of L. anserifera, L. anatifera, and the amphipods Caprella danilevskii and Jassa slatteryi, we created an equation to estimate minimum duration at sea. Predators such as the polychaete Amphinome rostrata may influence the biofouling community, as can beach scavengers once floating debris is cast ashore. We report a new maximum growth rate for L. anserifera of 1.45 mm−1, and our study is the first to report growth rates for any species of Lepas faster than 1 mm day−1. Lepas were larger on moored floats than on smaller, free-floating drifters. δ18O content of Lepas shells was a robust predictor of sea surface temperatures during formation for L. anatifera and L. anserifera. Our findings have important applications for estimating drift duration and trajectories of marine debris.